Acetazolamide in Central Sleep Apnea Patients Using Medication for Opioid Use Disorder

Impact of Acetazolamide on Central Sleep Apnea Patients Receiving Medication for Opioid Use Disorder

Patients with opioid use disorder treated with either methadone or buprenorphine are at risk of developing central sleep apnea (CSA) from these medications. Investigators will conduct a mechanistic trial using acetazolamide, a medicine known to improve CSA in other settings, to determine if acetazolamide can improve CSA due to medication for opioid use disorder and whether this leads to physiologic changes that might lead to reduced drug craving. Patients treated with medication for opioid use disorder and who have central sleep apnea will be randomized to treatment with acetazolamide or matching placebo for 7 days. At the end of the 7 days, they will undergo an overnight sleep study to assess the impact on breathing during sleep as well as sleep quality. In addition, measures of sympathetic tone, anxiety, arousal, cognition, and drug craving will be measured to determine if treatment of CSA with acetazolamide can produce physiologic changes that might contribute to improved health.

Study Overview

• Status: Recruiting
• Conditions: Central Sleep Apnea Comorbid With Opioid Use
• Intervention / Treatment: Drug: Acetazolamide; Drug: Placebo

Detailed Description

Medications used to treat opioid use disorder (MOUD) such as methadone and buprenorphine have been found to cause central sleep apnea (CSA), but the clinical ramifications are unclear. It has been hypothesized that the sleep fragmentation and intermittent hypoxemia caused by CSA from MOUD may lead to sympathetic activation, nocturnal arousal, increased anxiety, and cognitive impairment that may in turn increase drug craving and drug relapse. This mechanistic study will evaluate the potential adverse effect of CSA in patients on MOUD by evaluating the impact of acetazolamide to improve CSA and thereby lead to downstream physiologic changes in measures of sleep quality, sympathetic tone, nocturnal arousal, anxiety, cognitive functioning, and drug craving.

Eligible individuals will undergo an overnight research visit including overnight polysomnography, assessments of autonomic tone, sleep quality, nocturnal arousal, emotional distress, cognitive testing, and drug craving. Individuals with opioid-induced CSA will be randomized into a parallel-arm trial of acetazolamide vs. placebo with overnight research visit for outcome assessment at 7 days.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elizabeth Stempkowski; Phone Number: 412-648-9507; Email: stempkowskiem@upmc.edu
• Study Contact Backup: Name: Julia Sherman; Phone Number: 412-383-9469; Email: shermanj2@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Elizabeth Stempkowski; Phone Number: 412-648-9507; Email: stempkowskiem@upmc.edu
      • Principal Investigator: Sanjay R Patel, MD
      • Sub-Investigator: Venkatesh Krishnamurthy, MD
      • Sub-Investigator: Tae Woo Park, MD
      • Sub-Investigator: Kristine Wilckens, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients on Medication for Opioid Use Disorder (MOUD) with central sleep apnea.

Exclusion Criteria:

• Sleep-related Hypoventilation.
• Other causes of Central Sleep Apnea besides Opioid Use.
• Pregnancy.
• Contraindications for Acetazolamide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetazolamide; All participants in this group will receive one acetazolamide 250 mg pill in the evening for 7 days.	Drug: Acetazolamide; Oral acetazolamide 250 mg daily for 7 days
Placebo Comparator: Placebo; All participants in this group will receive one matching placebo pill in the evening for 7 days.	Drug: Placebo; Oral placebo daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Apnea Index (CAI)	The number of central apneas per hour of sleep, assessed by overnight polysomnography.; It can range from 0 to undefined events per hour.; Higher values indicate more severe central sleep apnea.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low frequency / high-frequency ratio (LF/HF ratio)	The ratio of low frequency to high frequency spectral power from heart rate variability analysis of electrocardiogram (ECG) collected during non-rapid eye movement (NREM) sleep on overnight polysomnography	7 days
Apnea Hypopnea Index (AHI)	The number of apneas plus hypopneas per hour of sleep on overnight polysomnography; It can range from 0 to undefined events per hour.; Higher values indicates severity of apneas and hypopneas.	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overnight urinary norepinephrine levels	Overnight urinary norepinephrine concentration normalized to urinary creatinine concentration	7 days
Pre-ejection period	Pre-ejection period assessed by impedance cardiography	7 days
Pre-sleep Arousal Scale (PSAS) score	16-item questionnaire assessing level of nocturnal arousal; It can range from 16 to 80.; Higher scores indicate higher levels of nocturnal arousal.	7 days
Arousal Index	The number of cortical arousals per hour of sleep on overnight polysomnography.; It can range from 0 to undefined events per hour.; Higher values indicate more severe sleep disturbance.	7 days
Generalized Anxiety Disorder 7 (GAD-7) score	7-item questionnaire assessing anxiety symptoms; It can range from 0 to 21.; Higher scores indicate more severe anxiety.	7 days
Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance score	t-score derived from 8-item PROMIS sleep disturbance questionnaire; Population mean is 50 and standard deviation is 10.; Higher values indicate greater levels of sleep disturbance.	7 days
Opioid cue-induced drug craving	The mean craving score reported after exposure to visual opioid cues relative to craving scores after viewing neutral cues.; Mean craving score ranges from 0 to 10.; Higher scores indicate higher level of drug craving.	7 days

Collaborators and Investigators

• Sponsor: Sanjay R Patel
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Sanjay R Patel, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: July 19, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Acetazolamide; Opioid Use Disorder; Methadone; Buprenorphine; Medication for opioid use disorder (MOUD)
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Thiadiazoles; Acetazolamide
• Other Study ID Numbers: STUDY23100016; R01DA059465 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual Participant Data (IPD) from this clinical trial will be shared with other researchers. The IPD to be shared includes final closed dataset (after de-identification). All data will be released according to the specific timelines stated in the National Institutes of Health (NIH) Policy, ensuring no compromise to privacy, confidentiality, proprietary interests, national security, or law enforcement activities. These data will be submitted to a NIH-funded data registry for data sharing purposes.
• IPD Sharing Time Frame: The IPD will become available within 1 year of analysis of primary outcome. This data will be accessible on an NIH-sponsored platform for as long as the agency maintains it.
• IPD Sharing Access Criteria: IPD will be available through a NIH funded registry. Access to the IPD will be governed by the policies and procedures of NIH.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No